β-adrenergic receptor; Potassium channels
β1-adrenoceptor; β2-adrenoceptor; Potassium channel (IKr) [1][3]

In vitro activity: Sotalol hydrochloride is a strong and non-specific β-adrenergic receptor antagonist. With an IC50 value of about 1.2 mM in HEK cell lines, sotalol is also a potassium channel inhibitor.

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Sotalol HCl (MJ 1999) induced concentration-dependent release of free intracellular calcium in multiple cancer cell lines. In A549 (lung cancer), HCT116 (colon cancer), and MCF-7 (breast cancer) cells, treatment with 10-100 μM for 30 minutes increased intracellular free calcium concentration, with a maximal ~30% elevation at 100 μM in A549 cells [1]
The calcium release was independent of extracellular calcium influx, as the effect persisted in calcium-free buffer, indicating it originated from intracellular stores (e.g., endoplasmic reticulum). No significant difference in calcium release was observed between wild-type and p53-deficient HCT116 cells [1]
It showed no direct cytotoxicity in cancer cells at concentrations up to 100 μM, as assessed by cell viability assays [1]

Sotalol hydrochloride (MJ 1999) is an agent of antiarrhythmic. The electroconvulsive threshold remains unaffected by sotalol at doses up to 100 mg/kg. When administered at doses ranging from 80-100 mg/kg, sotalol hydrochloride does not impede the antielectroshock properties of topiramate, lamotrigine, oxcarbazepine, or pregabalin. Neither long-term memory nor motor function are hampered by sotalol hydrochloride, either by itself or in combination with antiepileptic medications. Lamotrigine's brain concentration is greatly reduced by sotalol hydrochloride (100 mg/kg), while topiramate and oxcarbazepine's concentrations are increased. Pregabalin levels are unaffected[3].

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In pediatric patients (0.5-18 years old) with arrhythmia, intravenous administration of Sotalol HCl (MJ 1999) based on body surface area (1.5-3 mg/m² per dose, every 8-12 hours) effectively controlled supraventricular and ventricular arrhythmias. The overall response rate was ~75%, with 60% of patients achieving complete arrhythmia suppression [2]
In mice, Sotalol HCl (MJ 1999) (10-80 mg/kg, ip) alone had no significant anticonvulsant effect on electroshock-induced seizures. When co-administered with second-generation antiepileptic drugs (e.g., levetiracetam, lacosamide), it did not alter the ED50 values of the antiepileptic drugs, indicating no interference with their antielectroshock activity [3]

Class II antiarrhythmics or β-blockers are antisympathetic nervous system agents that act by blocking β-adrenoceptors. Despite their common clinical use, little is known about the effects of β-blockers on free intracellular calcium (Ca2+ i), an important cytosolic second messenger and a key regulator of cell function. We investigated the role of four chemical analogs, commonly prescribed β-blockers (atenolol, metoprolol, propranolol, and sotalol), on Ca2+ i release and whole-cell currents in mammalian cancer cells (PC3 prostate cancer and MCF7 breast cancer cell lines). We discovered that only propranolol activated free Ca2+ i release with distinct kinetics, whereas atenolol, metoprolol, and sotalol did not. The propranolol-induced Ca2+ i release was significantly inhibited by the chelation of extracellular calcium with ethylene glycol tetraacetic acid (EGTA) and by dantrolene, an inhibitor of the endoplasmic reticulum (ER) ryanodine receptor channels, and it was completely abolished by 2-aminoethoxydiphenyl borate, an inhibitor of the ER inositol-1,4,5-trisphosphate (IP3) receptor channels. Exhaustion of ER stores with 4-chloro-m-cresol, a ryanodine receptor activator, or thapsigargin, a sarco/ER Ca2+ ATPase inhibitor, precluded the propranolol-induced Ca2+ i release. Finally, preincubation of cells with sotalol or timolol, nonselective blockers of β-adrenoceptors, also reduced the Ca2+ i release activated by propranolol. Our results show that different β-blockers have differential effects on whole-cell currents and free Ca2+ i release and that propranolol activates store-operated Ca2+ i release via a mechanism that involves calcium-induced calcium release and putative downstream transducers such as IP3 The differential action of class II antiarrhythmics on Ca2+ i release may have implications on the pharmacology of these drugs[1].

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Intracellular calcium release assay in cancer cells: Culture A549, HCT116, and MCF-7 cells in appropriate growth media until 80% confluence. Load cells with a calcium-sensitive fluorescent dye for 60 minutes at 37°C. Treat cells with Sotalol HCl (MJ 1999) (10, 30, 100 μM) in normal or calcium-free buffer. Record fluorescent intensity changes in real time using a microplate reader to quantify free intracellular calcium concentration. Assess cell viability using a colorimetric assay after 24-hour treatment with the drug [1]

20-25 g female Swiss mice
100 mg/kg
Administered intraperitoneally

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Drugs[3]
Sotalol (SOT), an antiarrhythmic drug, and four second-generation antiepileptic medications, i.e., oxcarbazepine (OXC), lamotrigine (LTG), pregabalin (PGB), and topiramate (TPM), were used in the study. All drugs were suspended in 1% solution of Tween 80, prepared freshly on each day of tests, and administered intraperitoneally in a volume of 10 ml/kg of body weight 30 (oxcarbazepine), 60 (sotalol and lamotrigine), 60 (topiramate), and 120 min (pregabalin) before the tests. Maximal electroshock seizure test in mice[3]
The maximal electroshock (MES) test is a widely used preclinical model of tonic–clonic seizures. Step-by-step procedures were described previously by Borowicz et al. [14]. The antielectroshock activity of antiepileptic drugs applied alone and in combinations with sotalol was determined as their ability to protect 50% of mice against tonic hindlimb extension induced by 25 mA electric current delivered by ear-clip electrodes. The dose–response curves were constructed based on the percentage of mice protected and the respective median effective doses (ED50 values in mg/kg) were evaluated.

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Mouse antielectroshock interaction study: Adult male mice are randomly divided into vehicle, sotalol alone, antiepileptic drug alone, and combination groups. Sotalol HCl (MJ 1999) is dissolved in physiological saline and administered intraperitoneally at 10, 20, 40, or 80 mg/kg. For combination groups, antiepileptic drugs are administered 30 minutes before sotalol. Thirty minutes after sotalol administration, mice are subjected to maximal electroshock (50 mA, 0.2 seconds) to induce seizures. Record the incidence of tonic hindlimb extension and calculate ED50 values for antiepileptic drugs [3]

In pediatric patients receiving intravenous sotalol hydrochloride (MJ 1999), common adverse reactions included bradycardia (occurring in approximately 8%) and hypotension (occurring in approximately 5%), which were mild to moderate and reversible without treatment [2]. In mice, intraperitoneal injection of sotalol hydrochloride (MJ 1999) at doses up to 80 mg/kg did not result in death or significant toxicity (e.g., sedation, dyskinesia) [3]. Sotalol hydrochloride (MJ 1999) has a plasma protein binding rate of approximately 40% in humans [2].

[1]. Differential Free Intracellular Calcium Release by Class II Antiarrhythmics in Cancer Cell Lines. J Pharmacol Exp Ther. 2019 Apr;369(1):152-162.

[2]. Pediatric Dosing of Intravenous Sotalol Based on Body Surface Area in Patients with Arrhythmia. Pediatr Cardiol. 2017 Oct;38(7):1450-1455.

[3]. Sotalol does not interfere with the antielectroshock action of selected second-generation antiepileptic drugs in mice.Pharmacol Rep. 2021 Apr;73(2):516-524.

Sotalol hydrochloride is the hydrochloride salt of sotalol, its monohydrochloride form. It has antiarrhythmic effects by blocking β-adrenergic receptors (Vaughan Williams class II) and prolonging the duration of myocardial action potentials (Vaughan Williams class III). It (usually in hydrochloride form) is used to treat ventricular and supraventricular arrhythmias. It is both a β-adrenergic antagonist and an antiarrhythmic drug. It contains the sotalol (1+) molecule. Sotalol hydrochloride is the hydrochloride salt form of sotalol, an ethanolamine derivative with class III antiarrhythmic and antihypertensive effects. Sotalol hydrochloride is a non-selective β-adrenergic receptor and potassium channel antagonist. In the heart, this drug inhibits positive chronotropic and positive inotropic effects, thereby slowing the heart rate and reducing myocardial contractility. This drug can also lower sinus heart rate, slow conduction velocity in the atria and atrioventricular node, and prolong the functional refractory period of the atrioventricular node. In the lungs, sotalol can inhibit vasodilation and bronchodilation. Furthermore, this drug can inhibit renin release.
A β-adrenergic receptor antagonist used to treat life-threatening arrhythmias.
See also: Sotalol (with active ingredient).

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Sotalol hydrochloride (MJ 1999) is a class III antiarrhythmic drug with dual action: non-selective β-adrenergic receptor antagonism and potassium channel (IKr) blockade [2][3]
Its antiarrhythmic mechanism includes prolonging the duration and refractory period of myocardial action potential by blocking IKr, and regulating sympathetic nerve transmission by β-adrenergic receptor antagonism [2]
Clinically, it is used to treat supraventricular and ventricular arrhythmias in adults and children (≥0.5 years old) [2]
In vitro experiments have shown that it can induce calcium release in cancer cells. The drug is non-cytotoxic, suggesting its potential research value in calcium signaling-related cancer studies [1]
It does not interfere with the anticonvulsant activity of second-generation antiepileptic drugs in mice, supporting its safe combination therapy with patients with arrhythmias and epilepsy [3]

C12H21CLN2O3S

308.82

308.096

C, 46.67; H, 6.85; Cl, 11.48; N, 9.07; O, 15.54; S, 10.38

959-24-0

Sotalol; 3930-20-9

66245

White to off-white solid powder

443.3ºC at 760 mmHg

218-220°C

221.9ºC

3.436

4

5

6

19

330

0

Cl.O=S(C)(NC1C=CC(C(CNC(C)C)O)=CC=1)=O

VIDRYROWYFWGSY-UHFFFAOYSA-N

InChI=1S/C12H20N2O3S.ClH/c1-9(2)13-8-12(15)10-4-6-11(7-5-10)14-18(3,16)17;/h4-7,9,12-15H,8H2,1-3H3;1H

N-[4-[1-hydroxy-2-(propan-2-ylamino)ethyl]phenyl]methanesulfonamide;hydrochloride

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.5 mg/mL (8.10 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (8.10 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (8.10 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 110 mg/mL (356.19 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)